Synthetic or natural drugs aim to serve as remedies or preventive agents for illnesses and can be administered into the body by methods such as injection or ingestion. In comparing the various routes of drug administration available, ingestion or oral administration is preferred as it is less painful and has a higher rate of patient compliance. It is also a more convenient and simple or uncomplicated method as compared to injection.
More often than not, many poorly water-soluble drugs are the keys to treatment for many diseases. Thus, it is an arduous task and challenge for scientists to formulate a method for the generation of these drugs to improve their solubility within the human body. Further, water-insoluble drugs have low bioavailability. Ultimately, it would be ideal for drugs to have as high a level of bioavailability in the body as possible. However, when a poorly water-soluble drug is consumed orally, its bioavailability in vivo may be compromised due to incomplete absorption and first-pass metabolism in a patient's stomach. Hence, its medicinal purpose would not be as effective when consumed. As a result, it is desirable to maximize the bioavailability of drugs in vivo.
In recent years, research has been undertaken to develop alternate processes to generate nanoparticulate drugs in a bid to rectify the problem of poorly water-soluble drugs. Accordingly, the reduction of particle size can increase dissolution rate, and hence increase bioavailability. This is seen in a known method such as physical grinding in which nanoparticles are reduced from a big size to a smaller size in a media-milling step. However, a problem posed by this method is that it is very time consuming, and hence, it is an inconvenient method of producing nanoparticles. Another problem with this process is that the nanoparticles tend to agglomerate, leading to the growth of nanoparticles, which may result in instability of the nanoparticles.
Another known method relates to a combination of solid dispersion and spray granulation techniques. More particularly, it relates to a process for the preparation of a particulate material by controlled agglomeration method that enables a controlled growth in particle size. This method is especially suitable for use in the preparation of pharmaceutical compositions containing a therapeutically and/or prophylactically active substance which has a relatively low aqueous solubility and/or which is subjected to chemical decomposition. However, this method is not suitable for drugs which have a high melting-point.
Another known method relates to a process for producing a solid dispersion of an active ingredient which comprises feeding the active ingredient and an excipient to an extruder and forming a uniform extrudate. One disadvantage of this method is that a high temperature of the extruder barrel would be needed when the active ingredient has a high melting point in order to attain adequate dispersion of the active ingredient. This would inevitably lead to higher energy costs.
Further, other disadvantages of using solid dispersion of an active ingredient include the inability to scale-up bench-top formulations to manufacturing-sized batches; difficulty in controlling physicochemical properties of the drug; difficulty in delivering solid dispersion formulations as tablet or capsule dosage forms; the need for special handling and storage conditions of the formed drug due to its inability to withstand high temperatures; and instability of the drug and/or the formulation itself.
Another known method for producing drug nanoparticles involves the use of a supercritical fluid, such as supercritical carbon dioxide, to precipitate out drug nanoparticles dissolved in a solvent. The drug nanoparticles are then encapsulated in a polymer by using a non-aqueous solid-oil-oil-oil solid dispersion technique. However, due to the use of a supercritical fluid, high pressures that are in excess of 10 kPa are generally required in order to preserve the supercritical conditions of the supercritical fluid. As such, this method increases the operation costs required due to the use of specialized equipment needed to handle the supercritical fluids and can result in potential safety issues due to the high pressures involved. This method is also highly inflexible because the type of supercritical fluids that is suitable for use in such process is extremely limited.
Another method involved the use of an emulsion containing one or more compounds to be solidified in its dispersed phase and dosing this emulsion with an antisolvent in order to force the compounds to solidify from the emulsion. A disadvantage of this method is that due to the inherent incompatibility of the materials, substantial amounts of emulsifiers are necessary in order to form a stable emulsion. The size of the droplets is highly dependent on the system so that the particle size of the drug particles formed from this process cannot be accurately and adequately controlled. Further, the use of large amounts of emulsifiers could induce undesirable side-effects and is particularly undesirable in the manufacturing or formulation of active pharmaceutical compounds.
Furthermore, a common disadvantage with most of the above methods is the problem of scaling up production to an industrial scale in the pharmaceutical industry.
Therefore, there is a need to provide a process of making drugs nanoparticles that overcomes, or at least ameliorates, one or more of the problems and disadvantages described above.
There is also a need to provide drug nanoparticles that are suitable for oral administration to a patient diagnosed with a disease that requires the use of poorly-soluble drugs for treatment.